Article
Microbiology
Michael G. Whitfield, David M. Engelthaler, Christopher Allender, Megan Folkerts, Tim H. Heupink, Jason Limberis, Robin M. Warren, Annelies Van Rie, John Z. Metcalfe
Summary: This study investigated the diagnostic accuracy of pyrazinamide susceptibility testing and found a low prevalence of pyrazinamide heteroresistance in tuberculosis isolates.
JOURNAL OF CLINICAL MICROBIOLOGY
(2022)
Article
Microbiology
Kun Li, Zhongping Yang, Jing Gu, Ming Luo, Jiaoyu Deng, Yaokai Chen
Summary: This study identified and analyzed pncA gene mutations in Mycobacterium tuberculosis isolates from Chongqing, China, revealing 124 mutation types, including 30 new mutations. By analyzing mutations and pyrazinamidase activity, 322 isolates out of 424 drug-resistant isolates were predicted to be resistant to PZA.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Samuel J. Modlin, Tyler Marbach, Jim Werngren, Mikael Mansjo, Sven E. Hoffner, Faramarz Valafar
Summary: This study identified ClpC1 mutations associated with PZA resistance for the first time, with ClpC1(Val63Ala) mutation being overrepresented in Indo-Oceanic isolates with potential low-level PZA resistance. Genetic background plays an important role in the development of resistance.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Dian Ayu Eka Pitaloka, Arfan Arfan, Dwi Syah Fitra Ramadhan, Lidya Chaidir
Summary: This study aims to evaluate the impact of mutations found in pyrazinamide monoresistant strains of Mycobacterium tuberculosis on the effectiveness of pyrazinamide for tuberculosis treatment. Five mutations of pyrazinamidase were analyzed, and the results showed that three of these mutations affected the enzyme's activity and led to PZA resistance. However, the other two mutations had no effect. Experimental clarification is needed for further studies on drug resistance in pyrazinamidase.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Dipti Shrestha, Bhagwan Maharjan, Jeewan Thapa, Mwangala Lonah Akapelwa, Precious Bwalya, Joseph Yamweka Chizimu, Chie Nakajima, Yasuhiko Suzuki
Summary: This study collected information on pyrazinamide (PZA) susceptibility in Mycobacterium tuberculosis (MTB) isolates from Nepal by analyzing the pncA gene and its regulatory region. The study found an increasing level of PZA resistance in drug-resistant tuberculosis (DR-TB) in Nepal, emphasizing the importance of PZA susceptibility testing before DR-TB treatment.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Biology
Fahad M. Alshabrmi, Eid A. Alatawi
Summary: The evolution of MDR and XDR-TB is a growing concern and public health safety threat around the world. Gene mutations are the prime cause of drug resistance in tuberculosis, however the reports of double mutations further aggravated the situation. Structural bioinformatics approaches were used to understand the impact of novel mutations and design novel drugs for improved clinical outcome.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Microbiology
Simone Mok, Emma Roycroft, Peter R. Flanagan, Lorraine Montgomery, Emanuele Borroni, Thomas R. Rogers, Margaret M. Fitzgibbon
Summary: Combining genotypic and phenotypic drug susceptibility testing methods is necessary for accurate detection of PZA resistance in Mycobacterium tuberculosis isolates.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Yang Che, Dingyi Bo, Xiang Lin, Tong Chen, Tianfeng He, Yi Lin
Summary: In Ningbo, a high prevalence of PZA resistance among MDR-TB isolates was observed, with mutations in the pncA gene being the primary mechanism. DNA sequencing of pncA gene showed high sensitivity and specificity, providing rapid detection evidence for PZA drug resistance in MDR-TB cases in Ningbo.
BMC INFECTIOUS DISEASES
(2021)
Article
Infectious Diseases
Eva Sodja, Simon Koren, Natasa Toplak, Sara Truden, Manca Zolnir-Dovc
Summary: This study investigated the feasibility of full-length analysis of a gene linked with pyrazinamide (PZA) resistance using Ion Torrent technology and its comparison with phenotypic drug susceptibility testing (DST) in clinical tuberculosis (TB) isolates from the Balkan Peninsula. The results showed high agreement and sensitivity between NGS and conventional DST methods in detecting PZA resistance.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2022)
Article
Multidisciplinary Sciences
Nomonde Ritta Mvelase, Ravesh Singh, Khine Swe Swe-Han, Koleka Patience Mlisana
Summary: In rifampicin discordant tuberculosis isolates, the prevalence of pyrazinamide resistance is low, indicating the continued importance of this anti-TB drug in the treatment of these patients. Isoniazid susceptible isolates are unlikely to be resistant to pyrazinamide among the rifampicin discordant TB isolates.
Article
Infectious Diseases
Sirus Amini, Jalil Kardan-Yamchi, Hossein Kazemian, Mohammad Javad Nasiri, Gholamreza Hamzehloo, Sven Hoffner, Mohammad Mehdi Feizabadi
Summary: The study aimed to establish a reliable agar-based proportion method for detection of PZA-resistant phenotypes using Middlebrook 7H11 agar supplemented with calf bovine serum (CBS) compared with albumin/dextrose/catalase (ADC) enrichment and pncA/rpsA sequencing results. 7H11 agar supplemented with CBS showed greater sensitivity and accuracy in detecting PZA resistance compared to ADC, making it a less expensive and reliable testing method.
MICROBIAL DRUG RESISTANCE
(2021)
Article
Medicine, Research & Experimental
V. V. Sinkov, I. G. Kondratov, O. B. Ogarkov, S. N. Zhdanova, N. A. Sokolnikova, P. A. Khromova, E. A. Orlova, L. V. Rychkova, L. I. Kolesnikova
Summary: Pyrazinamide plays a crucial role in tuberculosis treatment. However, current microbiological tests for pyrazinamide resistance lack reliability due to the need for pH 5.5 pathogen growth. Genetic identification of drug resistance-causing mutations may offer a substitute. We have developed a software that interprets and predicts pyrazinamide resistance through Sanger sequencing. Comparing 16 clinical samples, our method showed significant advantages over single microbiological studies in reliability, regardless of isolate purity.
BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE
(2023)
Article
Chemistry, Medicinal
Renier van der Westhuyzen, Amanda Mabhula, Paul M. Njaria, Rudolf Mueller, Denis Ngumbu Muhunga, Dale Taylor, Nina Lawrence, Mathew Njoroge, Christel Brunschwig, Atica Moosa, Vinayak Singh, Srinivasa P. S. Rao, Ujjini H. Manjunatha, Paul W. Smith, Digby F. Warner, Leslie J. Street, Kelly Chibale
Summary: Screening of a library of small polar molecules against Mycobacterium tuberculosis led to the identification of potent benzoheterocyclic oxime carbamate hit series. Medicinal chemistry progression and structure-activity relationship studies were carried out to identify a compound for concept validation studies and define a lead optimization strategy. In vivo evaluation revealed carbamates may act as prodrugs, suggesting a novel and unknown mode of action for these antitubercular hits.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Ali A. Rabaan, Abbas Al Mutair, Hawra Albayat, Jawaher Alotaibi, Tarek Sulaiman, Mohammed Aljeldah, Basim R. Al Shammari, Amal H. Alfaraj, Mona A. Al Fares, Sara Alwarthan, Abdulwahab Z. Binjomah, Mohammed S. Alzahrani, Hatem M. Alhani, Mohammed S. Almogbel, Abdulmonem A. Abuzaid, Ghaya Alqurainees, Fatimah Al Ibrahim, Ali H. Alhaddad, Mubarak Alfaresi, Nadira Al-baghli, Saad Alhumaid
Summary: Mycobacterium tuberculosis, a pathogen causing tuberculosis, has caused millions of deaths and an increase in drug resistance. The COVID-19 pandemic has worsened the diagnosis and treatment of tuberculosis, resulting in more deaths and a decrease in newly diagnosed cases. Collaborative efforts have led to advancements in drug resistance detection methods and the development of new drugs against drug-resistant tuberculosis.
Article
Microbiology
Samuel J. Modlin, Afif Elghraoui, Deepika Gunasekaran, Alyssa M. Zlotnicki, Nicholas A. Dillon, Nermeeta Dhillon, Norman Kuo, Cassidy Robinhold, Carmela K. Chan, Anthony D. Baughn, Faramarz Valafar
Summary: Accurate and timely functional genome annotation of Mycobacterium tuberculosis virulent type strain H37Rv is achieved by systematic literature curation and structure-function inference, leading to valuable insights that can be applied in clinical and basic research. The updated annotations provide functional information for poorly characterized genes and proteins, improving the understanding of drug resistance, host immunity, and metabolism in tuberculosis research. This integrated approach highlights the translational value of combining structural modeling and systematic literature curation for studying various functions and pathways in microorganisms.
